PROJECT SUMMARY/ABSTRACT Hematological malignancies are the commonest childhood tumors, and despite remarkable advances in survival rates, remain a leading cause of cancer death. The last decade has witnessed great progress in understanding the genetic basis of these tumors, but translating these discoveries into mechanistic insight into the basis of tumorigenesis and treatment response, and into new diagnostic and therapeutic approaches remains limited. Advancing outcomes for children with hematologic malignancies is reliant on training independent investigators with expertise in genomic analysis, experimental modeling, translational science and preclinical modeling of childhood hematological malignancies. Although some T32 training program provide training in childhood cancer, none are solely devoted to training in hematological malignancies or a training program that utilizes the rich foundation of genomic discoveries from the Pediatric Cancer Genome Project. The proposed training program will equip the next generation of scientists with the skills and knowledge from multiple disciplines to become leaders in the field of childhood hematological malignancy research. The proposed program will train three postdoctoral fellows in the first three years, and four fellows in years four and five, with an additional position supported by St Jude. The program will provide an enriched training experience supported by faculty with diverse expertise, including mentorship teams for each trainee consisting of scientific and clinical investigators; a T32 Internal Executive Committee that reviews program progress and assists with training program development and coordination of training activities; an External Advisory Committee comprised of five national leaders in childhood cancer research and postdoctoral training; a dedicated lecture/seminar series providing training in genomics, genetics, pathology, biostatistics, experimental modeling, genome editing, immunotherapy, preclinical studies and clinical trial design; a trainee day featuring trainee and invited speaker presentations; training in scientific and grant writing; the requirement that trainees submit external grant funding applications no later than the second year of the fellowship; and detailed evaluation of the progress of trainees. Trainees will be closely integrated with the rich portfolio of basic to translational research activities of the St Jude Comprehensive Cancer Center Hematological Malignancies Program, which coordinates translation of basic science discoveries to clinical trials. This program will provide an unrivalled opportunity to train scientists to address critical unmet needs in childhood hematological malignancies.